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  • 1. Aldén, Anna
    et al.
    Ohlson, Sten
    Påhlsson, Peter
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology.
    Rydén, Ingvar
    HPLC analysis of carbohydrate deficient transferrin isoforms isolated by the Axis-Shield %CDT method2005In: Clinica Chimica Acta, ISSN 0009-8981, E-ISSN 1873-3492, Vol. 356, no 1-2, p. 143-146Article in journal (Refereed)
    Abstract [en]

    Background: Carbohydrate-deficient transferrin (CDT) is elevated during prolonged overconsumption of alcohol and CDT is considered to be the most specific biochemical marker for alcohol overconsumption. However, an accurate method for analysing CDT is necessary because the test is frequently used for example in legal matters. Methods: Patient serum samples were analysed with the Axis-Shield %CDT and eluates were pooled together. Transferrin was purified from the pool by affinity chromatography and further analysed with HPLC to determine the ratios of different transferrin isoforms. Results: In the eluates using the Axis-Shield %CDT method, a substantial amount of trisialo transferrin was found, which is generally not considered a CDT isoform. Conclusions: The fact that trisialo transferrin is present may generate falsely elevated CDT results and it could at least partly explain the discrepancy between results of the Axis-Shield %CDT assay and HPLC in routine analysis. © 2005 Elsevier B.V. All rights reserved.

  • 2.
    Alehagen, Urban
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Cardiology. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Goetze, JP
    Dahlström, Ulf
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Cardiology. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Reference intervals and decision limits for B-type natriuretic peptide (BNP) and its precursor (Nt-proBNP) in the elderly2007In: Clinica Chimica Acta, ISSN 0009-8981, E-ISSN 1873-3492, Vol. 382, no 1-2Article in journal (Refereed)
    Abstract [en]

    Background: Elderly patients have the highest prevalence of heart failure (HF). The aims of the study were to establish a reference interval for B-type natriuretic peptide (BNP) and (Nt-proBNP) in elderly people, and to identify clinically relevant decision limits based on long-term outcome. Methods: Plasma concentrations of BNP and Nt-proBNP were measured from two elderly populations: 218 healthy subjects (mean age 73 years, population I), and 474 patients (mean age 73 years, population II) with symptoms associated with HF. Study population II was followed for 6 years with registration of all cardiovascular mortality. Results: An association between both BNP and Nt-proBNP concentrations and age was found. The upper limit for the reference intervals in the healthy elderly (population I) was: BNP ≤ 28 pmol/L (≤ 97 ng/L), and Nt-proBNP ≤ 64 pmol/L (≤ 540 ng/L). Based on cardiovascular mortality, decision limits for BNP (∼ 50 pmol/L, ∼ 170 ng/L) and Nt-proBNP (∼ 200 pmol/L, ∼ 1700 ng/L) (population II) were determined. Conclusions: Besides establishing reference intervals for BNP and Nt-proBNP in an elderly population, a higher clinically relevant decision limit for BNP and Nt-proBNP was identified, indicating additive prognostic information of the peptides on top of measurements by echocardiography. Therefore, both reference intervals and decision limits should be included in clinical practice. © 2007.

  • 3. Boalth, Nicolas
    et al.
    Wandrup, Jesper
    Larsson, Lasse
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Clinical Chemistry. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Frischauf, Peter
    Lundsgaard, Finn
    Andersen, Willy
    Jensen, Niels-Henrik
    Singer, Rolf
    Troldborg, Carl
    Lunding, Gitte
    Blood gases and oximetry: calibration-free new dry-chemistry and optical technology for near-patíent testing.2001In: Clinica Chimica Acta, ISSN 0009-8981, E-ISSN 1873-3492, Vol. 307, p. 225-233Article in journal (Refereed)
  • 4. Burnett, Robert W
    et al.
    D'Orazio, Paul
    Fogh-Andersen, Niels
    Kuwa, Katsuhiko
    Külpmann, Wolf
    Larsson, Lasse
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Clinical Chemistry. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Lewnstam, Andrzej
    Maas, Anton
    Mager, Gerhard
    Spichiger-Keller, Ursula
    IFCC recommendation on reporting results for blood glucose.2001In: Clinica Chimica Acta, ISSN 0009-8981, E-ISSN 1873-3492, Vol. 307, p. 205-209Article in journal (Refereed)
  • 5.
    Enocsson, Helena
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Sjöwall, Christoffer
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Rheumatology.
    Wetterö, Jonas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Soluble urokinase plasminogen activator receptor: A valuable biomarker in systemic lupus erythematosus?2015In: Clinica Chimica Acta, ISSN 0009-8981, E-ISSN 1873-3492, Vol. 444, p. 234-241Article, review/survey (Refereed)
    Abstract [en]

    Systemic lupus erythematosus (SLE) is a potentially severe autoimmune condition with an unpredictable disease course, often with fluctuations in disease activity over time. Long term inflammation and drug-related side-effects may subsequently lead to permanent organ damage, a consequence which is intimately connected to decreased quality of life and mortality. New lupus biomarkers that convey information regarding inflammation and/or organ damage are thus warranted. Today, there is no clinical biomarker that indicates the risk of damage accrual. Herein we highlight the urokinase plasminogen activator receptor (uPAR) and especially its soluble form (suPAR) that besides having biological functions in e.g. proteolysis, cell migration and tissue homeostasis, recently has emerged as a promising biomarker of inflammation and prognosis of several disorders. A strong association between suPAR and organ damage in SLE was recently demonstrated, and preliminary data (presented in this review) suggests the possibility of a predictive value of suPAR blood levels. The involvement of suPAR in the pathogenesis of SLE remains obscure, but its effects in leukocyte recruitment, phagocytic uptake of dying cells (efferocytosis) and complement regulation suggests that the central parts of the SLE pathogenesis could be regulated by suPAR, and vice versa.

  • 6.
    Hannestad, Ulf
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry.
    Theodorsson, Elvar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Evengard, B.
    Evengård, B., Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital, Huddinge, SE-141 86 Stockholm, Sweden.
    ß-Alanine and ?-aminobutyric acid in chronic fatigue syndrome2007In: Clinica Chimica Acta, ISSN 0009-8981, E-ISSN 1873-3492, Vol. 376, no 1-2, p. 23-29Article in journal (Refereed)
    Abstract [en]

    Background: Due to the occurrence of sleep disturbances and fatigue in chronic fatigue syndrome (CFS), an investigation was performed to examine if there is an abnormal excretion of ?-aminobutyric acid (GABA) and/or its structural analogue ß-alanine in the urine from CFS patients. Both GABA and ß-alanine are inhibitory neurotransmitters in the mammalian central nervous system. Methods: The 24 h urine excretion of GABA and ß-alanine was determined by isotope dilution gas chromatography mass spectrometry in 33 CFS patients and 43 healthy controls. The degree of symptoms in both patients and controls was measured by grading of three typical CFS symptoms using a Visual Analogue Scale. Results: Men had a significantly higher excretion of both ß-alanine and GABA than women. Comparing CFS patients with healthy controls showed no significant difference in excretion of neither ß-alanine nor GABA. No correlation was found between the excretion of ß-alanine or GABA and any of the three characteristic CFS symptoms measured. However, two female and two male CFS patients excreted considerably higher amounts of ß-alanine in their 24 h urine samples than control subjects. Conclusions: Increased excretion of ß-alanine was found in a subgroup of CFS patients, indicating that there may be a link between CFS and ß-alanine in some CFS patients. © 2006 Elsevier B.V. All rights reserved.

  • 7.
    Landberg, Eva
    et al.
    Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry. Linköping University, Faculty of Health Sciences.
    Wahlberg Topp, Jeanette
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Endocrinology and Gastroenterology UHL.
    Rydén, Ingvar
    Division of Clinical Chemistry, Kalmar County Hospital, Kalmar, Sweden.
    Arvidsson, Britt-Marie
    Division of Clinical Chemistry, Kalmar County Hospital, Kalmar, Sweden.
    Ekman, Bertil
    Linköping University, Department of Medicine and Care, Internal Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Endocrinology and Gastroenterology UHL.
    Detection of molecular variants of prolactin in human serum, evaluation of a method based on ultrafiltration2007In: Clinica Chimica Acta, ISSN 0009-8981, E-ISSN 1873-3492, Vol. 376, no 1-2, p. 220-225Article in journal (Refereed)
    Abstract [en]

    Background

    In human blood, there are several molecular variants of prolactin with different biological effects. There is a need for new methods to detect and quantify these variants in order to fully understand the pathophysiological role of prolactin.

    Methods

    A method based on ultrafiltration was optimized, validated and compared to PEG precipitation. Serum samples from 84 patients were analyzed before and after pre treatment on two immunoassays, Elecsys (Roche) and Access (Beckman). Protein G precipitation was used to confirm presence of macroprolactin.

    Results

    The recovery of prolactin after ultrafiltration was lower than after PEG precipitation. A limit of 40% recovery after PEG precipitation corresponded to 27% recovery after ultrafiltration. Using these limits there were total agreement regarding detection of macroprolactin (rs = 0.96). In contrast, recovery of prolactin in samples without macroprolactin showed a considerable disagreement between ultrafiltration and PEG precipitation (rs = 0.48). Within-run CV was 4% for the ultrafiltration method. The correlation coefficient (r) between the immunoassays was 0.96 after ultrafiltration.

    Conclusions

    Ultrafiltration can be used to compare different prolactin immunoassays and to detect macroprolactin in assays with interference from PEG. For samples without macroprolactin ultrafiltration may give additional information reflecting individual variations of other molecular variants of prolactin.

  • 8.
    Landberg, Eva
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Diagnostics, Department of Clinical Chemistry.
    Åström, Eva
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Kågedal, Bertil
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Diagnostics, Department of Clinical Chemistry.
    Påhlsson, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Disialo–trisialo bridging of transferrin is due to increased branching and fucosylation of the carbohydrate moiety2012In: Clinica Chimica Acta, ISSN 0009-8981, E-ISSN 1873-3492, Vol. 414, p. 58-64Article in journal (Refereed)
    Abstract [en]

    Background

    Carbohydrate deficient transferrin (CDT) is used for detection of alcohol abuse and follow-up. High performance liquid chromatography (HPLC) of transferrin glycoforms is highly specific for identification of alcohol abuse, but unresolved disialo- and trisialotransferrin glycoforms sometimes makes interpretation difficult. The cause of this phenomenon is unknown, cannot be explained by genetic variants of transferrin, but seems to be associated with liver disease.

    Methods

    Nineteen serum samples showing di–tri bridging when analyzed by HPLC were collected. Transferrin was purified by affinity chromatography, and N-linked oligosaccharides were released enzymatically. The N-glycans were further analyzed by high performance anion-exchange chromatography with pulsed amperometric detection and MALDI-TOF mass spectrometry.

    Results

    The HPLC-analysis showed three different types of glycoform patterns. The N-glycans from fifteen samples showed patterns with increased number of triantennary structures containing one or two fucose residues. One sample contained an increased amount of triantennary glycans without fucose. Three samples showed a glycosylation pattern similar to normal transferrin.

    Conclusions

    The di–tri bridging phenomenon was associated with alterations in transferrin glycosylation in the majority of cases. Transferrin contained a higher extent of triantennary and often fucosylated N-linked oligosaccharides. These results may be important in future diagnostic approaches to liver diseases.

  • 9.
    Löfman, Owe
    et al.
    Linköping University, Department of Biomedicine and Surgery, Clinical Chemistry. Linköping University, Department of Medicine and Care, Internal Medicine. Östergötlands Läns Landsting, Centre for Public Health Sciences, Centre for Public Health Sciences. Linköping University, Faculty of Health Sciences.
    Magnusson, Per
    Linköping University, Department of Biomedicine and Surgery, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
    Toss, Göran
    Linköping University, Department of Medicine and Care, Internal Medicine. Linköping University, Faculty of Health Sciences.
    Larsson, Lasse
    Linköping University, Department of Biomedicine and Surgery, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
    Common biochemical markers of bone turnover predict future bone loss: A 5-year follow-up study2005In: Clinica Chimica Acta, ISSN 0009-8981, E-ISSN 1873-3492, Vol. 356, no 1-2, p. 67-75Article in journal (Refereed)
    Abstract [en]

    Background

    Bone mineral density (BMD) is used to follow gain or loss of bone mass but cannot detect changes within a short period of time. Biochemical markers of bone turnover may be of value for prediction of individual bone loss.

    Methods

    We studied the relation between common inexpensive markers of bone turnover (serum alkaline phosphatase (ALP), osteocalcin (OC), urinary hydroxyproline (OHPr), and calcium (Ca)), BMD, age, and menopause in a combined cross-sectional and longitudinal design comprising 429 pre- and postmenopausal randomly selected women aged 21–79 years (mean 50 years). A follow-up was initiated after 5 years (including 192 of these women), which focused on changes in bone mass and the ability of these four common markers of bone turnover (sampled at baseline) to predict future bone loss.

    Results

    A marked increase was observed for all markers at the beginning of menopause. During the postmenopausal period ALP and Ca decreased to near premenopausal levels, while OC and OHPr remained high even 15 years after menopause. We also found inverse correlations at baseline between the bone markers and BMD, independent of the selected marker or skeletal site, r=−0.14 to −0.46, P<0.05. The correlations between ALP, OC, OHPr, and subsequent bone loss over 5 years, was significant for arm, r=−0.23 to −0.36, P<0.01. Baseline levels of all bone markers correlated significantly at group level with the 5-year follow-up of BMD for all sites. The ability of markers to predict individual bone loss was estimated by a multivariate regression model, which included baseline BMD, age, and body mass index as independent variables. ROC analysis showed a validity of approximately 76% for the forearm model, but was lower for the hip (55%) and lumbar spine (65%).

    Conclusions

    These data show that the common inexpensive biochemical markers of bone turnover ALP, OC, OHPr, and Ca were related to the current bone mass and, moreover, provides information about future bone loss at the individual level. Future investigations should include an evaluation of the clinical relevance of markers of bone turnover in relation to fracture risk.

  • 10.
    Magnusson, Per
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Clinical Chemistry. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Sharp, Christopher
    Farley, John
    Different distributions of human bone alkaline phosphatase isoforms in serum and bone tissue extracts2002In: Clinica Chimica Acta, ISSN 0009-8981, E-ISSN 1873-3492, Vol. 325, no 1-2, p. 59-70Article in journal (Refereed)
    Abstract [en]

    Background: In vitro, bone alkaline phosphatase (BALP) is released from the osteoblast membrane with its glycosylphosphatidylinositol (GPI) anchor still attached (i.e., in an anchor-intact form), however, in vivo, BALP circulates as a variable mixture of anchorless isoforms, which can be identified by high-performance liquid chromatography (HPLC). Previous studies have shown that the relative abundance of these BALP isoforms in serum may be clinically useful for the diagnosis and management of metabolic bone disease. Methods: In the current studies, we describe a method for the determination of anchorless BALP isoforms in extracts of bone and we present novel data on the conversion of anchor-intact to anchorless BALP by incubation with endogenous circulating GPI-specific phospholipase D (GPI-PLD). Results: A 72-h extraction with 0.1% Triton X-100 released approximately 90% of the BALP activity from powdered bone. An average of 19% of this activity was anchorless, but essentially all of the activity could be converted to the anchorless form by incubation with partially purified GPI-PLD from human serum. Using HPLC, we detected four BALP isoforms (B/I, B1x, B1, and B2) in these GPI-PLD-treated extracts of bone. An additional BALP fraction was also detected in the samples during the initial phase of GPI-PLD treatment. Conclusions: The abundance of the BALP isoforms differed between bone and serum, particularly for the B/I isoform, which comprised, on average, 18% of the BALP in GPI-PLD-treated extracts of healthy bone tissue, but only 6% of the total BALP activity in serum from healthy individuals. Based on our recent finding of differences in the number of sialic acid residues between the BALP isoforms, we hypothesize that this difference between BALP isoforms in serum and extracts of bone is due to the different patterns of glycosylation, which results in different biological half-lives in the circulation. A preliminary application of our method to the extraction of BALP isoforms from a small number of human bone samples suggests that the method should be useful for studies of human skeletal site-specific and metabolic bone disease-specific differences in the amounts and distributions of the BALP isoforms in bone.

  • 11.
    Milovanovic, Micha
    et al.
    Östergötlands Läns Landsting, Local Health Care Services in East Östergötland, Department of Internal Medicine in Norrköping.
    Nillsson, Ethel
    Östergötlands Läns Landsting, Local Health Care Services in East Östergötland, Department of Internal Medicine in Norrköping.
    Järemo, Petter
    Östergötlands Läns Landsting, Local Health Care Services in East Östergötland, Department of Internal Medicine in Norrköping.
    Relationships between platelets and inflammatory markers in rheumatoid arthritis2004In: Clinica Chimica Acta, ISSN 0009-8981, E-ISSN 1873-3492, Vol. 343, no 1-2, p. 237-240Article in journal (Refereed)
    Abstract [en]

    AIM OF THE STUDY: To investigate platelets and different inflammatory markers in conjunction with a substantial inflammatory reaction. We used individuals with active rheumatoid arthritis (RA) as an experimental cohort.

    METHODS: We selected 16 patients with active RA having at least one affected joint. On day 1, platelet and neutrophil counts together with C-reactive protein (CRP) were determined. We further analysed platelet volume (MPV) and plasma levels of thrombopoietin (TPO), P-selectin, myeloperoxidase and interleukin 6 (IL-6). After 2 years when all patients failed to show any swollen joints all analyses were repeated.

    RESULTS AND CONCLUSIONS: As expected platelet count, CRP and IL-6 were elevated in active RA. The measures correlated with each other thus reflecting the same characteristic of the inflammatory response. The neutrophil count, MPV and myeloperoxidase also mirror disease activity. They failed to correlate with other activity markers thus providing unique information. MPV and myeloperoxidase on day 1 correlated with recovery values. Therefore, they could be suitable to use when following the inflammatory reaction over a long period of time.

  • 12.
    Milovanovic, Micha
    et al.
    Linköping University, Department of Social and Welfare Studies, Health, Activity, Care. Linköping University, Faculty of Health Sciences.
    Nillsson, Ethel
    Linköping University, Department of Clinical and Experimental Medicine, Rheumatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in the East of Östergötland.
    Järemo, Petter
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in the East of Östergötland, Department of Internal Medicine VHN.
    Relationships between platelets and inflammatory markers in rheumatoid arthritis2004In: Clinica Chimica Acta, ISSN 0009-8981, E-ISSN 1873-3492, Vol. 343, no 1-2, p. 237-240Article in journal (Refereed)
    Abstract [en]

    Aim of the study: To investigate platelets and different inflammatory markers in conjunction with a substantial inflammatory reaction. We used individuals with active rheumatoid arthritis (RA) as an experimental cohort. Methods: We selected 16 patients with active RA having at least one affected joint. On day 1, platelet and neutrophil counts together with C-reactive protein (CRP) were determined. We further analysed platelet volume (MPV) and plasma levels of thrombopoietin (TPO), P-selectin, myeloperoxidase and interleukin 6 (IL-6). After 2 years when all patients failed to show any swollen joints all analyses were repeated. Results and conclusions: As expected platelet count, CRP and IL-6 were elevated in active RA. The measures correlated with each other thus reflecting the same characteristic of the inflammatory response. The neutrophil count, MPV and myeloperoxidase also mirror disease activity. They failed to correlate with other activity markers thus providing unique information. MPV and myeloperoxidase on day 1 correlated with recovery values. Therefore, they could be suitable to use when following the inflammatory reaction over a long period of time.

  • 13.
    Mårdh, Erik
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology.
    Mårdh, Sven
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology.
    Mårdh, Bibbi
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology.
    Borch, Kurt
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Surgery. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Diagnosis of gastritis by means of a combination of serological analyses2002In: Clinica Chimica Acta, ISSN 0009-8981, E-ISSN 1873-3492, Vol. 320, no 1-2, p. 17-27Article in journal (Refereed)
    Abstract [en]

    Background: Gastroscopy and examination of biopsy is normally required for diagnosis of gastritis. This is costly and inconvenient for the patient, and there is a need for a simple pregastroscopic screening method to reduce the endoscopy workload. Our aim was to develop a serological screening test for gastritis. Methods: Sera from subjects examined with gastroscopy and biopsy were analyzed for H,K-ATPase antibodies, Helicobacter pylori antibodies and pepsinogen I. The diagnoses were normal gastric mucosa (n=50), duodenal ulcer (n=53) and atrophic corpus gastritis, with (n=50) or without pernicious anemia (n=46). Results: An evaluation scheme was constructed to optimize the diagnostic agreement between serology and gastric mucosal morphology. The sensitivity to detect gastritis was 98% (146/149) (95% CI 94-100%) and the specificity 84% (42/50) (95% CI 71-93%). Additional sera from 483 subjects from the general population were analyzed. There was a good agreement between serology and gastric mucosal morphology. Conclusions: Assays of multiple serum analytes are useful for the initial screening of gastritis. They are complementary to upper gastroscopy by identification of subjects with a normal gastric mucosa, those who qualify for eradication of H. pylori, and those who have developed atrophy and are at risk of developing malignancy and, therefore, require gastroscopic examination.

  • 14.
    Nezirevic Dernroth, Dzeneta
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Årstrand, Kerstin
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
    Greco, Giorgia
    Department of Organic Chemistry and Biochemistry, University of Naples Federico II, Complesso Universitario Monte S. Angelo, Via Cyntia 4 I-80126, Naples Italy.
    Panzella, Lucia
    Department of Organic Chemistry and Biochemistry, University of Naples Federico II, Complesso Universitario Monte S. Angelo, Via Cyntia 4 I-80126, Naples Italy.
    Napolitano, Alessandra
    Department of Organic Chemistry and Biochemistry, University of Naples Federico II, Complesso Universitario Monte S. Angelo, Via Cyntia 4 I-80126, Naples Italy.
    Kågedal, Bertil
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Pheomelanin-related benzothiazole isomers in the urine of patients with diffuse melanosis of melanoma2010In: Clinica Chimica Acta, ISSN 0009-8981, E-ISSN 1873-3492, Vol. 411, no 17-18, p. 1195-1203Article in journal (Refereed)
    Abstract [en]

    Currently used as structural markers for pheomelanin identification and quantitation, benzothiazole compounds derived from isomeric cysteinyldopas have been indicated by recent in vitro studies as new potential pheomelanogenesis intermediates. Prompted by previous reports on the occurrence of large amounts of 5-S-cysteinyldopa (5-S-CD) and trichochromes in urine of patient with diffuse melanosis of melanoma we investigated the presence of benzothiazole compounds in the urine of these patients.

    Hydrophilic interaction liquid chromatography on zwitterionic stationary phase (ZIC-HILIC) and photo-diode array (PDA) detection was used for analysis of 6-(2-amino-2-carboxyethyl)-4-hydroxybenzothiazole-2-carboxylic acid (BTCA-5), and 7-(2-amino-2-carboxyethyl)-4-hydroxybenzothiazole-2-carboxylic acid (BTCA-2), derived from 5-S-CD and 2-S-cysteinyldopa (2-S-CD) isomers, respectively. Isocratic mobile phase with minimal sample preparation allowed efficient separation of the compounds, which were safely identified by their typical absorption features.

    Among 21 melanoma patients examined three showed diffuse melanosis. The levels of urinary BTCAs were found to be highly associated with melanosis but more loosely to excreted 5-S-CD. Analysis of the pigmented fraction of urine following alkaline hydrogen peroxide degradation and quantitation of BTCAs provided evidence for the presence of pheomelanins at higher levels in patients with melanosis.

  • 15.
    Rydén, Ingvar
    et al.
    Department of Clinical Chemistry, Kalmar County Hospital, Sweden.
    Påhlsson, Peter
    Linköping University, Department of Biomedicine and Surgery, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
    Lundblad, Arne
    Linköping University, Department of Biomedicine and Surgery, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
    Skogh, Thomas
    Linköping University, Department of Molecular and Clinical Medicine, Rheumatology. Linköping University, Faculty of Health Sciences.
    Fucosylation of α1-acid glycoprotein (orosomucoid) compared with traditional biochemical markers of inflammation in recent onset rheumatoid arthritis2002In: Clinica Chimica Acta, ISSN 0009-8981, E-ISSN 1873-3492, Vol. 317, no 1-2, p. 221-229Article in journal (Refereed)
    Abstract [en]

    Background: Fucosylation of α1-acid glycoprotein (AGP, orosomucoid) has previously been found to be increased in patients with rheumatoid arthritis. Furthermore, the degree of fucosylation has been suggested to reflect disease activity. Therefore, we investigated the fucosylation of AGP in 131 patients (96 women and 35 men) with recent onset rheumatoid arthritis (RA). We compared the results with traditional biochemical markers of inflammation, i.e. plasma concentrations of AGP (P-AGP), and C-reactive protein (P-CRP).

    Methods: AGP fucosylation measured with a novel lectin enzyme-linked immunosorbent assay (ELISA) was compared with a disease activity score (DAS28) and its components, and with P-AGP, and P-CRP at the time of diagnosis, and at a follow-up visit 1 year later.

    Results: Both men and women with RA had increased AGP fucosylation compared to healthy individuals. We found a weak correlation between AGP fucosylation and DAS28 only in men. In men with initially increased AGP fucosylation, the level of fucosylation correlated with the change in DAS28 during the first year following diagnosis.

    Conclusion: We conclude that AGP fucosylation is not superior to traditional markers of disease activity in RA. However, AGP fucosylation may give some additional information to traditional biochemical markers on the disease progression in men.

  • 16.
    Shamoun, Levar
    et al.
    Reg Jonkoping Cty, Sweden.
    Skarstedt, Marita
    Reg Jonkoping Cty, Sweden.
    Andersson, Roland
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Reg Jonkoping Cty, Sweden.
    Wågsäter, Dick
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Dimberg, Jan
    Jonkoping Univ, Sweden.
    Association study on IL-4, IL-4R alpha and IL-13 genetic polymorphisms in Swedish patients with colorectal cancer2018In: Clinica Chimica Acta, ISSN 0009-8981, E-ISSN 1873-3492, Vol. 487, p. 101-106Article in journal (Refereed)
    Abstract [en]

    Background: Interleukin 4 (IL-4) and interleukin 13 (IL-13) are anti-inflammatory and immunomodulatory cytokines which share a common cellular receptor IL4R alpha and are involved in the same signaling pathways. Our purpose was to assess whether genetic variants within IL-4, IL-13 and IL-4R alpha are associated with the risk or clinical outcome of colorectal cancer (CRC). Methods: Three single nucleotide polymorphisms (SNPs) were screened in 466 patients with CRC and 445 healthy controls. The selected SNPs were IL-4 SNP rs2243250, IL-4R alpha SNP rs1801275 and IL-13 SNP rs1800925. Results: We found that the genotype variant T/T in IL-13 gene was associated with a higher risk of CRC. Kaplan Meier analysis showed that the cancer specific survival differed between C/C and CT + TT for IL-4 SNP. Moreover, the carriers of the T allele were associated with the highest risk of CRC death with a hazard ratio (HR) of 1.57, 95% CI 1.06-2.36, p = -.024. The observed effect of the T allele was restricted to stage III patients. Conclusion: Our results indicate IL-13 SNP rs1800925 as a risk factor for CRC and that IL-4 SNP rs2243250 could be a useful prognostic marker in the follow-up and clinical management of patients with CRC especially in stage III disease.

  • 17. Sharp, Christopher A
    et al.
    Linder, Cecilia
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Magnusson, Per
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Analysis of human bone alkaline phosphatase isoforms: Comparison of isoelectric focusing and ion-exchange high-performance liquid chromatography2007In: Clinica Chimica Acta, ISSN 0009-8981, E-ISSN 1873-3492, Vol. 379, no 1-2, p. 105-112Article in journal (Refereed)
    Abstract [en]

    Background: Several isoforms of alkaline phosphatase (ALP) can be identified in human tissues and serum after separation by anion-exchange HPLC and isoelectric focusing (IEF). Methods: We purified four soluble bone ALP (BALP) isoforms (B/I, B1x, B1 and B2) from human SaOS-2 cells, determined their specific pI values by broad range IEF (pH 3.5-9.5), compared these with commercial preparations of bone, intestinal and liver ALPs and established the effects of neuraminidase and wheat germ lectin (WGA) on enzyme activity. Results: Whilst the isoforms B1x (pI = 4.48), B1 (pI = 4.32) and B2 (pI = 4.12) resolved as well-defined bands, B/I resolved as a complex (pI = 4.85-6.84). Neuraminidase altered the migration of all BALP isoforms to pI = 6.84 and abolished their binding to the anion-exchange matrix, but increased their enzymatic activities by 11-20%. WGA precipitated the BALP isoforms in IEF gels and the HPLC column and attenuated their enzymatic activities by 54-73%. IEF resolved the commercial BALP into 2 major bands (pI = 4.41 and 4.55). Conclusions: Migration of BALP isoforms is similar in IEF and anion-exchange HPLC and dependent on sialic acid content. HPLC is preferable in smaller scale research applications where samples containing mixtures of BALP isoforms are analysed. Circulating liver ALP (pI = 3.85) can be resolved from BALP by either method. IEF represents a simpler approach for routine purposes even though some overlapping of the isoforms may occur. © 2007 Elsevier B.V. All rights reserved.

  • 18.
    Sjöwall, Christoffer
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Rheumatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Rheumatology in Östergötland.
    Wetterö, Jonas
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Rheumatology.
    Pathogenic implications for autoantibodies against C-reactive protein and other acute phase proteins2007In: Clinica Chimica Acta, ISSN 0009-8981, E-ISSN 1873-3492, Vol. 378, no 1-2, p. 13-23Article in journal (Refereed)
    Abstract [en]

    Systemic lupus erythematosus (SLE) is a systemic rheumatic disease characterized clinically by multiorgan involvement and serologically by the occurrence of antinuclear antibodies. SLE patients may present with multiple autoantibodies to cytoplasmic and cell surface antigens as well as to circulating plasma proteins. Another feature of SLE is that serum levels of C-reactive protein (CRP) often remain low despite high disease activity and despite high levels of other acute phase proteins and interleukin-6, i.e. the main CRP inducing cytokine. Apart from its important role as a laboratory marker of inflammation, CRP attracts increasing interest due to its many intriguing biological functions, one of which is a role as an opsonin contributing to the elimination of apoptotic cell debris, e.g. nucleosomes, thereby preventing immunization against autoantigens. Recently, autoantibodies against CRP and other acute phase proteins have been reported in certain rheumatic conditions, including SLE. Although the presence of anti-CRP autoantibodies does not explain the failed CRP response in SLE, antibodies directed against acute phase proteins have several implications of pathogenetic interest. This paper thus highlights the biological and clinical aspects of native and monomeric CRP and anti-CRP, as well as autoantibodies against mannose-binding lectin, serum amyloid A and serum amyloid P component. © 2006 Elsevier B.V. All rights reserved.

  • 19.
    Sun, Yi-Qian
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of surgery.
    Monstein, Hans-Jurg
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Molecular Biological Techniques.
    Ryberg, Anna
    Borch, Kurt
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of surgery. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Multiple strand displacement amplification of DNA isolated from human archival plasma/serum: Identification of cytokine polymorphism by pyrosequencing analysis2007In: Clinica Chimica Acta, ISSN 0009-8981, E-ISSN 1873-3492, Vol. 377, no 1-2, p. 108-113Article in journal (Refereed)
    Abstract [en]

    Background: DNA isolation from formalin-fixed paraffin-embedded tissue appears to be problematic due to degradation caused by fixative. Our aim was to investigate if the isolated genomic DNA from archival plasma/serum, combined with multiple strand displacement amplification (MDA) can be used for genotyping. Methods: Nine archival plasma/serum samples and freshly frozen gastric biopsies from the same nine H. pylori-infected subjects were used for DNA isolation. Subsequently, MDA-DNA derived from the plasma/serum samples and DNA isolated from the antrum biopsies were analyzed by PCR amplification and pyrosequencing for the presence of interleukin-1beta gene (IL-1B) single nucleotide polymorphism (SNP). In addition, Southern blot and pyrosequencing analysis of H. pylori-specific PCR amplicons were performed. Results: IL-1B SNP profiles obtained from the plasma/serum MDA-DNA and antrum biopsy DNA were identical. A C/C genotype was observed in 7 of 9 samples, and 2 of 9 revealed a C/T genotype for IL-1B - 511. Similarly, 7 of 9 had a T/T, and 2 of 9 had a C/T genotype for IL-1B - 31, 4 of 9 had a C/C, 4 of 9 had a C/T, and 1 of 9 had a T/T genotype, respectively, for IL-1B + 3954. Moreover, pyrosequencing analysis revealed the presence of H. pylori 26695 and J99-like 16S rDNA variable V3 region sequence motifs in the antrum biopsies but not in the plasma/serum samples. Conclusions: We conclude that MDA combined with pyrosequencing enables a rapid and accurate molecular typing of cytokine single nucleotide polymorphisms from archival plasma/serum samples. © 2006 Elsevier B.V. All rights reserved.

  • 20.
    Wetterö, Jonas
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Rheumatology . Linköping University, Faculty of Health Sciences.
    Nilsson, Lennart
    Linköping University, Department of Medicine and Health Sciences, Cardiology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Jonasson, Lena
    Linköping University, Department of Medicine and Health Sciences, Cardiology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Sjöwall, Christoffer
    Linköping University, Department of Clinical and Experimental Medicine, Rheumatology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Rheumatology in Östergötland.
    Reduced serum levels of autoantibodies against monomeric C-reactive protein (CRP) in patients with acute coronary syndrome2009In: Clinica Chimica Acta, ISSN 0009-8981, E-ISSN 1873-3492, Vol. 400, no 1-2, p. 128-131Article in journal (Refereed)
    Abstract [en]

    Introduction: Inflammation is pivotal in atherosclerosis. Minor C-reactive protein (CRP) response reflects low-grade vascular inflammation and the high-sensitivity CRP test with levels >= 3.0 mg/l predicts coronary vascular events and survival in angina pectoris as well as in healthy subjects. We and others recently reported autoantibodies against monomeric CRP (anti-CRP) in rheumatic conditions, e.g. systemic lupus erythematosus (SLE), and a connection between anti-CRP and cardiovascular disease in SLE has been suggested.

    Patients and methods: Anti-CRP serum levels were determined with ELISA in 140 individuals; 50 healthy controls and 90 patients with angiographically verified coronary artery disease of which 40 presented with acute coronary syndrome (ACS) and 50 with stable angina pectoris (SA).

    Results: Significantly lower anti-CRP levels were observed in ACS compared to SA and controls (p=0.019). ACS patients, who had not been prescribed statins before their respective cardiovascular event, had lower anti-CRP (p = 0.049). BMI correlated directly to anti-CRP levels in cross section analysis (p = 0.043), but there was no association between anti-CRP and smoking or cholesterol.

    Discussion: In ACS, it is plausible that ruptured plaques and inflamed tissue may be more prone to opsonization by monomeric CRP leading to consumption of anti-CRP, Hypothetically, surface-bound anti-CRP could thereby enhance the local inflammation in plaques.

  • 21.
    Åvall Lundqvist, Elisabeth
    et al.
    Department of Obstetrics and Gynecology, Karolinska Hospital, Stockholm, Sweden.
    Sjövall, K
    Department of Obstetrics and Gynecology, Karolinska Hospital, Stockholm.
    Eneroth, P H
    Unit for applied biochemistry, Clinical research center, Huddinge Hospital, Stockholm, Sweden.
    Influences of diet and surgical trauma on serum alkaline DNase activity levels.1992In: Clinica Chimica Acta, ISSN 0009-8981, E-ISSN 1873-3492, Vol. 205, no 1-2Article in journal (Refereed)
    Abstract [en]

    Changes in serum alkaline DNase activities might predict the therapeutic response in various malignant diseases. A decrease in serum alkaline DNase activity within days from the onset of therapy has been related to tumour necrosis and may be a possible sign of clinical response to effective treatment. To study if changes in serum alkaline DNase activity could be induced by non-tumour related tissue destruction, sera were collected on several occasions perioperatively in 18 patients undergoing surgery for benign gynaecological disease. Thirty apparently healthy women served as the control group. A significant decrease (P less than 0.001) in serum alkaline DNase activity was observed after an overnight fast in both groups of women. In contrast to the control women, the operated patients showed a significant decrease (P less than 0.001) in serum alkaline DNase activity throughout the operative period and 1 week postoperatively. We conclude that serum alkaline DNase activity is influenced by dietary factors as well as surgical trauma. These factors may limit the clinical usefulness of SADA in patients with cancer.

  • 22.
    Åvall-Lundqvist, Elisabeth
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Department of Obstetrics and Gynecology, Karolinska Hospital, Stockholm, Sweden.
    Economidou-Karaoglou, A
    Sjövall, K
    Lans, M
    Taper, H S
    Roberfroid, M
    Eneroth, P
    Serum alkaline DNase activity in normal or nonhospitalised individuals.1989In: Clinica Chimica Acta, ISSN 0009-8981, E-ISSN 1873-3492, Vol. 185, no 1, p. 35-43Article in journal (Refereed)
    Abstract [en]

    According to previous observations, the variations in serum alkaline DNase activity (SADA) appeared to be useful in monitoring malignant disease. In this study, SADA was measured in 625 individuals to explore nontumor-related factors which may influence SADA levels. The overall range in SADA was 0.2-82.3 kU/l. Women aged 50-79 years had higher (p less than 0.001) levels of SADA than younger females. A similar but less consistent effect of age was noticed in men (0.01 less than p less than 0.05). Older men had lower (0.01 less than p less than 0.05) SADA levels than the older women. Old women substituted with estrogens had lower (0.01 less than p less than 0.05) levels of SADA than those not treated with estrogens. SADA levels in pregnancy as well as postparturition were lower (p less than 0.001) than SADA values in nonpregnant females of similar age. In fertile women, no SADA variation was observed during the menstrual cycle and there was no significant effect of contraceptive pills. In males, SADA seemed unrelated to testosterone or cortisol levels but varied during the day. Smoking, alcohol consumption and drug therapy appeared to be without effect on SADA.

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